Type I allergy represents an immunologically-mediated hypersensitivity disease which affects almost 25% of the population worldwide [1]. Allergic patients suffer from the increased and inappropriate production of IgE antibodies against otherwise harmless antigens (pollen-, mite-, mould-, hair/dander-allergens) [1, 2]. Allergen-mediated crosslinking of IgE antibodies bound to effector cells (e. g., mast calls, basophils) via FcεRI induces the immediate release of biologically active mediators (histamine, leukotrienes) and causes the acute symptoms of atopy (e.g., allergic rhinitis, conjunctivitis, asthma and anaphylactic shock) [3]. When allergens are presented via IgE-FcεRI on professional antigen-presenting cells (e.g., monocytes, dendritic cells), T cells become activated and release Th2 cytokines thus leading to chronic, delayed disease manifestations (atopic dermatitis, chronic asthma) [4-6].
The interaction of allergens, allergen-specific IgE and FcεRI therefore represents a key pathomechanism in atopy and many forms of asthma. Since the identification and characterization of IgE antibodies [7, 8] and FcεRI [9], considerable effort has been spent in the analysis of their interactive domains and in particular to identify competitors of this interaction for a universal therapy of atopic disease [10]. Attempts to determine the interactive sites between human IgE and the alpha chain of FcεRI [11-14] comprised the screening of recombinant proteins/peptides [15-17], mutant proteins [14], chemically synthesized peptides [18, 19], and structural analyses [20]. Furthermore, attempts were made to induce autoantibody responses against the receptor binding site of IgE [21] in order to prevent IgE binding to FcεRI. Other therapeutic approaches comprise the development of IgE-derived peptides [15, 18, 19], nucleic acids [22] and humanized anti-IgE antibodies [23-25]. Most of the described competitors result from laborious structural and rationale design [19] combined with evaluation in sophisticated cellular assays (e.g., basophil histamine release) [26] or from extensive in vivo testing [27]. Although many compounds have been described sofar, there still remains a need of improvements within this area.